PROJECT SUMMARY Opioid use disorders (OUD) are among the most severe and deadly substance use disorders (SUD) in young people. Psychiatric disorders pose one of the major risks to develop opioid and other SUDs. For instance, young people with psychopathology are at two to three-fold increased risk to develop nicotine, alcohol, opioid and drug use disorders. Reciprocally, very high rates of psychopathology have been reported in samples of young people with OUD and other SUDs. This is particularly important since up to three-quarters of psychiatric and SUDs onset in childhood or young adulthood. Despite psychopathology robustly increasing the risk for later substance related disorders, remarkably little has been completed examining the impact of treating psychopathology on reducing rates of OUD, nicotine and other SUDs. Given the common prevalence of juvenile psychopathology, and the high morbidity and mortality associated with OUD and other SUDs, identification of substance use and psychopathology as well as elucidating the longer-term impacts, and intervening relationships, of treatment of psychopathology on OUD, nicotine and other SUDs in behavioral health and substance use settings in young people is of the highest clinical and public health utility. The main aims of this study are to implement a pragmatic set of office-based instrumentation using patient related outcome measures linked to electronic health records (EPIC) for intake and follow-up assessments to evaluate psychopathology, OUD, nicotine and other SUDs-as well as the cost-effectiveness of these interventions. We plan to study young people aged 16-30 years old who are receiving treatment naturalistically as part of their routine clinical care in behavioral health outpatient settings. We aim to compare those with higher- relative to lower-treatment exposure for up to 3.5 years to examine the effects of pharmacotherapy, psychosocial treatments, and their combination on the later development of OUD, nicotine and other SUDs in young people. Using identical methodology, in outpatient SUD treatment settings, we also plan to examine similar age patients with non-opioid SUD to examine the impact of treatment in mitigating the development of OUD. We also aim to examine important mediators and moderators of psychosocial factors and treatment response on later OUD, nicotine and other SUDs. Data derived from this study will help inform clinical guidelines, public health policy, and provide important secondary outcomes for further work on the prevention of OUD, nicotine and SUD in relation to early-onset psychopathology.